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Browsing by Author "Szer, Jeffrey"
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Item Fludarabine and Melphalan Compared with Reduced Doses of Busulfan and Fludarabine Improve Transplantation Outcomes in Older Patients with Myelodysplastic Syndromes(Elsevier, 2021) Oran, Betül; Ahn, Kwang Woo; Fretham, Caitrin; Beitinjaneh, Amer; Bashey, Asad; Pawarode, Attaphol; Wirk, Baldeep; Scott, Bart L.; Savani, Bipin N.; Bredeson, Christopher; Weisdorf, Daniel; Marks, David I.; Rizzieri, David; Copelan, Edward; Hildebrandt, Gerhard C.; Hale, Gregory A.; Murthy, Hemant S.; Lazarus, Hillard M.; Cerny, Jan; Liesveld, Jane L.; Yared, Jean A.; Yves-Cahn, Jean; Szer, Jeffrey; Verdonck, Leo F.; Aljur, Mahmoud; van der Poel, Marjolein; Litzow, Mark; Kalaycio, Matt; Grunwald, Michael R.; Diaz, Miguel Angel; Sabloff, Mitchell; Kharfan-Dabaja, Mohamed A.; Majhail, Navneet S.; Farhadfar, Nosha; Reshef, Ran; Olsson, Richard F.; Gale, Robert Peter; Nakamura, Ryotaro; Seo, Sachiko; Chhabra, Saurabh; Hashmi, Shahrukh; Farhan, Shatha; Ganguly, Siddhartha; Nathan, Sunita; Nishihori, Taiga; Jain, Tania; Agrawal, Vaibhav; Bacher, Ulrike; Popat, Uday; Saber, Wael; Medicine, School of MedicineReduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age ≥60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose ≤7.2 mg/kg or a low-dose melphalan total dose ≤150 mg/m2. The 2 groups, recipients of FluBu (n = 697) and recipients of FluMel (n = 448), were comparable in terms of disease- and transplantation-related characteristics except for the more frequent use of antithymocyte globulin or alemtuzumab in the FluBu group (39% versus 31%). The median age was 67 years in both groups. FluMel was associated with a reduced relapse incidence (RI) compared with FluBu, with a 1-year adjusted incidence of 26% versus 44% (P ≤ .0001). Transplantation-related mortality (TRM) was higher in the FluMel group (26% versus 16%; P ≤ .0001). Because the magnitude of improvement with FluMel in RI was greater than the improvement in TRM with FluBu, disease-free survival (DFS) was better at 1 year and beyond with FluMel compared with FluBu (48% versus 40% at 1 year [P = .02] and 35% versus 27% at 3 years [P = .01]). Overall survival was comparable in the 2 groups at 1 year (63% versus 61%; P = .4) but was significantly improved with FluMel compared with FluBu at 3 years (46% versus 39%; P = .03). Our results suggest that FluMel is associated with superior DFS compared with FluBu owing to reduced RI in older patients with MDS patients.Item The Role of Donor Lymphocyte Infusion (DLI) in Post Hematopoietic Cell Transplant (HCT) Relapse for Chronic Myeloid Leukemia (CML) in the Tyrosine Kinase Inhibitor (TKI) Era(Elsevier, 2020-06) Schmidt, Sarah; Liu, Ying; Hu, Zhen-Huan; Williams, Kirsten M.; Lazarus, Hillard M.; Vij, Ravi; Kharfan-Dabaja, Mohamed A.; Ortí, Guillermo; Wiernik, Peter H.; Weisdorf, Daniel; Kamble, Rammurti T.; Herzig, Roger; Wirk, Baldeep; Cerny, Jan; Bacher, Ulrike; Chaudhri, Naeem A.; Nathan, Sunita; Farhadfar, Nosha; Aljurf, Mahmoud; Gergis, Usama; Szer, Jeffrey; Seo, Sachiko; Hsu, Jack W.; Olsson, Richard F.; Maharaj, Dipnarine; George, Biju; Hildebrandt, Gerhard C.; Agrawal, Vaibhav; Nishihori, Taiga; Abdel-Azim, Hisham; Alyea, Edwin; Popat, Uday; Sobecks, Ronald; Scott, Bart L.; Holter Chakrabarty, Jennifer; Saber, Wael; Medicine, School of MedicineTreatment for relapse of chronic myeloid leukemia (CML) following hematopoietic cell transplantation (HCT) includes tyrosine kinase inhibitors (TKIs) with or without donor lymphocyte infusions (DLIs), but the most effective treatment strategy is unknown. This study was performed through the Center for International Blood and Marrow Transplant Research (CIBMTR) database. We retrospectively reviewed all patients reported to the CIBMTR registry from 2002 to 2014 who underwent HCT for CML and were alive 30 days postrelapse. A total of 215 HCT recipients relapsed and were analyzed in the following groups: (1) TKI alone (n = 128), (2) TKI with DLI (n = 48), and (3) DLI without TKI (n = 39). In multivariate analysis, disease status prior to HCT had a significant effect on overall survival (OS). Patients who received a DLI alone compared with a TKI with a DLI had inferior survival (hazard ratio, 2.28; 95% confidence interval, 1.23 to 4.24; P= .009). Those who received a TKI alone had similar survival compared with those who received a TKI with a DLI (P = .81). These data support that despite use of TKIs pretransplantation, TKI salvage therapy continues to provide significant survival following relapse in patients with CML following HCT. These data do not suggest that adding a DLI to a TKI adds an improvement in OS.